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Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain

Title:

Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain

Frederick, Ariana, Goldsmith, Jory, de Zavalia, Nuria and Amir, Shimon (2017) Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain. PLOS ONE, 12 (4). e0176279. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/journal.pone.0176279

Abstract

Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain. Regions examined included the limbic forebrain (dorsal striatum, nucleus accumbens, amygdala, stria terminalis), thalamus medial habenula of the thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in nearly all neurons (~90%), and PER2 was expressed in a slightly lower proportion of cells. There was no specific correlation to SubP- or Enk- expressing subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were expressed in a much smaller percentage of cells, and Enk was rarely found in the same cells that expressed the clock proteins (SubP was undetectable). These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Article
Refereed:Yes
Authors:Frederick, Ariana and Goldsmith, Jory and de Zavalia, Nuria and Amir, Shimon
Journal or Publication:PLOS ONE
Date:2017
Funders:
  • Concordia Open Access Author Fund
Digital Object Identifier (DOI):10.1371/journal.pone.0176279
ID Code:982563
Deposited By: Danielle Dennie
Deposited On:23 May 2017 16:15
Last Modified:18 Jan 2018 17:55

References:

1. Sukumaran S, Almon RR, DuBois DC, Jusko WJ. Circadian rhythms in gene expression: Relationship to physiology, disease, drug disposition and drug action. Adv Drug Deliv Rev. 2010;62(9–10):904–17. pmid:20542067

2. Videnovic A, Lazar AS, Barker RA, Overeem S. 'The clocks that time us'—circadian rhythms in neurodegenerative disorders. Nature reviews Neurology. 2014;10(12):683–93. Epub 2014/11/12. pmid:25385339

3. Silver R, Kriegsfeld LJ. Circadian rhythms have broad implications for understanding brain and behavior. Eur J Neurosci. 2014;39(11):1866–80. pmid:24799154

4. Colwell CS. Linking neural activity and molecular oscillations in the SCN. Nat Rev Neurosci. 2011;12(10):553–69. Epub 2011/09/03. pmid:21886186

5. Dibner C. On the robustness of mammalian circadian oscillators. Cell cycle. 2009;8(5):681–2. pmid:19223765

6. Harbour VL, Weigl Y, Robinson B, Amir S. Comprehensive mapping of regional expression of the clock protein PERIOD2 in rat forebrain across the 24-h day. PLoS One. 2013;8(10):e76391. Epub 2013/10/15. pmid:24124556

7. Namihira M, Honma S, Abe H, Tanahashi Y, Ikeda M, Honma K. Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats. Neurosci Lett. 1999;267(1):69–72. Epub 1999/07/10. pmid:10400251

8. Masubuchi S, Honma S, Abe H, Ishizaki K, Namihira M, Ikeda M, et al. Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats. Eur J Neurosci. 2000;12(12):4206–14. pmid:11122332

9. Shieh KR. Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK, in the rat brain. Neuroscience. 2003;118(3):831–43. Epub 2003/04/25. pmid:12710990

10. Asai M, Yoshinobu Y, Kaneko S, Mori A, Nikaido T, Moriya T, et al. Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats. J Neurosci Res. 2001;66(6):1133–9. pmid:11746446

11. Smarr BL, Jennings KJ, Driscoll JR, Kriegsfeld LJ. A time to remember: the role of circadian clocks in learning and memory. Behav Neurosci. 2014;128(3):283–303. pmid:24708297

12. Kafka MS, Benedito MA, Blendy JA, Tokola NS. Circadian rhythms in neurotransmitter receptors in discrete rat brain regions. Chronobiology international. 1986;3(2):91–100. pmid:2824075

13. Kafka MS, Benedito MA, Roth RH, Steele LK, Wolfe WW, Catravas GN. Circadian rhythms in catecholamine metabolites and cyclic nucleotide production. Chronobiology international. 1986;3(2):101–15. pmid:2824067

14. Castaneda TR, de Prado BM, Prieto D, Mora F. Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light. Journal of pineal research. 2004;36(3):177–85. Epub 2004/03/11. pmid:15009508

15. Amir S, Robinson B. Thyroidectomy alters the daily pattern of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats. Neurosci Lett. 2006;407(3):254–7. Epub 2006/09/16. pmid:16973268

16. Amir S, Lamont EW, Robinson B, Stewart J. A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci. 2004;24(4):781–90. Epub 2004/01/30. pmid:14749422

17. Lamont EW, Robinson B, Stewart J, Amir S. The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci U S A. 2005;102(11):4180–4. Epub 2005/03/05. pmid:15746242

18. Segall LA, Amir S. Exogenous corticosterone induces the expression of the clock protein, PERIOD2, in the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala of adrenalectomized and intact rats. J Mol Neurosci. 2010;42(2):176–82. Epub 2010/04/28. pmid:20422314

19. Segall LA, Perrin JS, Walker CD, Stewart J, Amir S. Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats. Neuroscience. 2006;140(3):753–7. http://dx.doi.org/10.1016/j.neuroscience.2006.03.037. pmid:16678973

20. Hood S, Cassidy P, Cossette MP, Weigl Y, Verwey M, Robinson B, et al. Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors. J Neurosci. 2010;30(42):14046–58. Epub 2010/10/22. pmid:20962226

21. Gravotta L, Gavrila AM, Hood S, Amir S. Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain. J Mol Neurosci. 2011;45(2):162–71. Epub 2011/04/13. pmid:21484443

22. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr. et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990;250(4986):1429–32. Epub 1990/12/07. pmid:2147780

23. Lu XY, Ghasemzadeh MB, Kalivas PW. Expression of D1 receptor, D2 receptor, substance P and enkephalin messenger RNAs in the neurons projecting from the nucleus accumbens. Neuroscience. 1998;82(3):767–80. Epub 1998/03/04. pmid:9483534

24. Day HE, Curran EJ, Watson SJ Jr, Akil H. Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1beta. The Journal of comparative neurology. 1999;413(1):113–28. Epub 1999/08/28. pmid:10464374

25. Swanson LW, Sawchenko PE. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annual review of neuroscience. 1983;6:269–324. Epub 1983/01/01. pmid:6132586

26. Ceccatelli S, Eriksson M, Hökfelt T. Distribution and Coexistence of Corticotropin-Releasing Factor-, Neurotensin-, Enkephalin-, Cholecystokinin-, Galanin- and Vasoactive Intestinal Polypeptide/Peptide Histidine Isoleucine-Like Peptides in the Parvocellular Part of the Paraventricular Nucleus. Neuroendocrinology. 1989;49(3):309–23. pmid:2469987

27. Vanderhaeghen JJ, Lotstra F, Liston DR, Rossier J. Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons. Proceedings of the National Academy of Sciences. 1983;80(16):5139–43.

28. Yamada K, Emson P, Hokfelt T. Immunohistochemical mapping of nitric oxide synthase in the rat hypothalamus and colocalization with neuropeptides. Journal of chemical neuroanatomy. 1996;10(3–4):295–316. Epub 1996/06/01. pmid:8811420

29. Olster DH, Blaustein JD. Immunocytochemical colocalization of progestin receptors and beta-endorphin or enkephalin in the hypothalamus of female guinea pigs. Journal of neurobiology. 1990;21(5):768–80. Epub 1990/07/01. pmid:2144316

30. Foo KS, Hellysaz A, Broberger C. Expression and colocalization patterns of calbindin-D28k, calretinin and parvalbumin in the rat hypothalamic arcuate nucleus. Journal of chemical neuroanatomy. 2014;61–62:20–32. Epub 2014/07/12. pmid:25014433

31. Everitt BJ, Meister B, Hokfelt T, Melander T, Terenius L, Rokaeus A, et al. The hypothalamic arcuate nucleus-median eminence complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons. Brain research. 1986;396(2):97–155. Epub 1986/06/01. pmid:2874874

32. Lecourtier L, Kelly PH. A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neuroscience and biobehavioral reviews. 2007;31(5):658–72. Epub 2007/03/24. pmid:17379307

33. Khachaturian H, Lewis ME, Hollt V, Watson SJ. Telencephalic enkephalinergic systems in the rat brain. J Neurosci. 1983;3(4):844–55. pmid:6834107

34. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed. SanDiego, CA: Academic Press; 1998.
35. Watson RE Jr, Wiegand SJ, Clough RW, Hoffman GE. Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides. 1986;7(1):155–9. pmid:3520509

36. Lee IT, Chang AS, Manandhar M, Shan Y, Fan J, Izumo M, et al. Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms. Neuron. 2015;85(5):1086–102. Epub 2015/03/06. pmid:25741729

37. Schnell SA, Staines WA, Wessendorf MW. Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem. 1999;47(6):719–30. pmid:10330448

38. Swanson LW. Brain maps: structure of the rat brain: a laboratory guide with printed and electronic templates for data, models, and schematics. Amsterdam; New York: Elsevier; 2004.

39. Gangarossa G, Espallergues J, de Kerchove d'Exaerde A, El Mestikawy S, Gerfen CR, Herve D, et al. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens. Frontiers in neural circuits. 2013;7:22. Epub 2013/02/21. pmid:23423476

40. Ikemoto S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain research reviews. 2007;56(1):27–78. Epub 2007/06/19. pmid:17574681

41. Alheid GF. Extended amygdala and basal forebrain. Annals of the New York Academy of Sciences. 2003;985:185–205. Epub 2003/05/02. pmid:12724159

42. Welsh DK, Takahashi JS, Kay SA. Suprachiasmatic nucleus: cell autonomy and network properties. Annual review of physiology. 2010;72:551–77. Epub 2010/02/13. pmid:20148688

43. Ferguson AV, Latchford KJ, Samson WK. The paraventricular nucleus of the hypothalamus—a potential target for integrative treatment of autonomic dysfunction. Expert opinion on therapeutic targets. 2008;12(6):717–27. Epub 2008/05/16. pmid:18479218

44. Joly-Amado A, Cansell C, Denis RG, Delbes AS, Castel J, Martinez S, et al. The hypothalamic arcuate nucleus and the control of peripheral substrates. Best practice & research Clinical endocrinology & metabolism. 2014;28(5):725–37. Epub 2014/09/27.

45. Chronwall BM. Anatomy and physiology of the neuroendocrine arcuate nucleus. Peptides. 1985;6 Suppl 2:1–11. Epub 1985/01/01.

46. Warden MK, Young WS. Distribution of cells containing mRNAs encoding substance P and neurokinin B in the rat central nervous system. The Journal of comparative neurology. 1988;272(1):90–113. pmid:2454979

47. Viswanath H, Carter AQ, Baldwin PR, Molfese DL, Salas R. The medial habenula: still neglected. Frontiers in human neuroscience. 2013;7:931. Epub 2014/01/31. pmid:24478666

48. Abe M, Herzog ED, Yamazaki S, Straume M, Tei H, Sakaki Y, et al. Circadian rhythms in isolated brain regions. J Neurosci. 2002;22(1):350–6. Epub 2002/01/05. pmid:11756518

49. Albanese A, Altavista MC, Rossi P. Organization of central nervous system dopaminergic pathways. J Neural Transm Suppl. 1986;22:3–17. pmid:3465873

50. Coronas V, Srivastava LK, Liang JJ, Jourdan F, Moyse E. Identification and localization of dopamine receptor subtypes in rat olfactory mucosa and bulb: a combined in situ hybridization and ligand binding radioautographic approach. Journal of chemical neuroanatomy. 1997;12(4):243–57. Epub 1997/05/01. pmid:9243344

51. Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA, et al. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proc Natl Acad Sci U S A. 1993;90(19):8861–5. Epub 1993/10/01. pmid:8415621

52. Gerfen CR, Young WS 3rd. Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain research. 1988;460(1):161–7. Epub 1988/09/13. pmid:2464402

53. Gangarossa G, Espallergues J, Mailly P, De Bundel D, de Kerchove d'Exaerde A, Herve D, et al. Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum. Frontiers in neural circuits. 2013;7:124. Epub 2013/08/03. pmid:23908605

54. Skoufias DA, Wilson L. Mechanism of inhibition of microtubule polymerization by colchicine: inhibitory potencies of unliganded colchicine and tubulin-colchicine complexes. Biochemistry. 1992;31(3):738–46. pmid:1731931

55. Liu B, Kwok RPS, Fernstrom JD. Colchicine-induced increases in immunoreactive neuropeptide levels in hypothalamus: Use as an index of biosynthesis. Life Sciences. 1991;49(5):345–52. http://dx.doi.org/10.1016/0024-3205(91)90441-D. pmid:1677440

56. Maywood ES, Reddy AB, Wong GK, O'Neill JS, O'Brien JA, McMahon DG, et al. Synchronization and maintenance of timekeeping in suprachiasmatic circadian clock cells by neuropeptidergic signaling. Current biology: CB. 2006;16(6):599–605. Epub 2006/03/21. pmid:16546085

57. Choi S, Wong LS, Yamat C, Dallman MF. Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator? J Neurosci. 1998;18.

58. Harbour V. Comprehensive mapping of PERIOD2 expression patterns in the rat forebrain across the 24-hr day. Montreal: Concordia University; 2011.

59. Reppert SM, Weaver DR. Molecular analysis of mammalian circadian rhythms. Annual review of physiology. 2001;63:647–76. Epub 2001/02/22. pmid:11181971

60. Yan L, Karatsoreos I, Lesauter J, Welsh DK, Kay S, Foley D, et al. Exploring spatiotemporal organization of SCN circuits. Cold Spring Harbor symposia on quantitative biology. 2007;72:527–41. Epub 2008/04/19. pmid:18419312

61. Guilding C, Hughes AT, Brown TM, Namvar S, Piggins HD. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus. Molecular Brain. 2009;2(1):28.

62. Uchida H, Nakamura TJ, Takasu NN, Todo T, Sakai T, Nakamura W. Cryptochrome-dependent circadian periods in the arcuate nucleus. Neuroscience Letters. 2016;610:123–8. http://dx.doi.org/10.1016/j.neulet.2015.10.071. pmid:26542738

63. Delezie J, Dumont S, Sandu C, Reibel S, Pevet P, Challet E. Rev-erbalpha in the brain is essential for circadian food entrainment. Scientific reports. 2016;6:29386. Epub 2016/07/07. pmid:27380954

64. Riddle M, Mezias E, Foley D, LeSauter J, Silver R. Differential localization of PER1 and PER2 in the brain master circadian clock. Eur J Neurosci. 2016. Epub 2016/10/16.

65. Tritsch NX, Sabatini BL. Dopaminergic modulation of synaptic transmission in cortex and striatum. Neuron. 2012;76(1):33–50. Epub 2012/10/09. pmid:23040805

66. Gallardo CM, Darvas M, Oviatt M, Chang CH, Michalik M, Huddy TF, et al. Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice. eLife. 2014;3:e03781. Epub 2014/09/14. pmid:25217530

67. Granados-Fuentes D, Saxena MT, Prolo LM, Aton SJ, Herzog ED. Olfactory bulb neurons express functional, entrainable circadian rhythms. Eur J Neurosci. 2004;19(4):898–906. Epub 2004/03/11. pmid:15009137

68. Granados-Fuentes D, Prolo LM, Abraham U, Herzog ED. The suprachiasmatic nucleus entrains, but does not sustain, circadian rhythmicity in the olfactory bulb. J Neurosci. 2004;24(3):615–9. Epub 2004/01/23. pmid:14736846

69. Granados-Fuentes D, Tseng A, Herzog ED. A circadian clock in the olfactory bulb controls olfactory responsivity. J Neurosci. 2006;26(47):12219–25. Epub 2006/11/24. pmid:17122046

70. Amir S, Cain S, Sullivan J, Robinson B, Stewart J. In rats, odor-induced Fos in the olfactory pathways depends on the phase of the circadian clock. Neurosci Lett. 1999;272(3):175–8. Epub 1999/10/03. pmid:10505609

71. Slotnick B. Animal cognition and the rat olfactory system. Trends Cogn Sci. 2001;5(5):216–22. Epub 2001/04/27. pmid:11323267

72. Davidson AJ, Aragona BJ, Werner RM, Schroeder E, Smith JC, Stephan FK. Food-anticipatory activity persists after olfactory bulb ablation in the rat. Physiol Behav. 2001;72(1–2):231–5. Epub 2001/03/10. pmid:11240001
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